Potent inhibition of hepatitis B virus production in vitro by modified pyrimidine nucleosides.
2',3'-Dideoxy-3'-fluorothymidine (FddThd), 2',3'-didehydro-2',3'- dideoxythymidine (ddeThd), and 3'-fluoro-5-methyl-deoxycytidine (FddMeCyt) are, in their triphosphate forms, selective inhibitors of human immunodeficiency virus type 1 reverse transcriptase. We report that 0.3 microM FddThd, FddMeCyt, or ddeThd as well as 3'-chloro-5-methyl-deoxycytidine (ClddMeCyt) or 3'-amino-5-methyl-deoxycytidine (AddMeCyt) almost completely blocked production of hepatitis B virus (HBV) particles by HBV DNA-transfected cell line 2.2.15 in vitro. Only at an at least 10-fold-higher concentration was a cytotoxic effect observed. These results indicate that FddThd, FddMeCyt, ClddMeCyt, AddMeCyt, and ddeThd are potent anti-HBV agents in vitro.
Matthes
E
E
Zentralinstitut für Molekularbiologie, Akademie der Wissenschaften der Deutschen Demokratischen Republik, Berlin-Buch, German Democratic Republic.
Langen
P
P
von Janta-Lipinski
M
M
Will
H
H
Schröder
H C
HC
Merz
H
H
Weiler
B E
BE
Müller
W E
WE
D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006824:Hybridization, Genetic / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000494:pharmacology*
D000998:Antiviral Agents; D004279:DNA, Viral; D011741:Pyrimidine Nucleosides